Good performance of p16/ki‐67 dual‐stained cytology for surveillance of women treated for high‐grade CIN

Women treated for high‐grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high‐risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki‐67 dual‐staine...

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Bibliographic Details
Published in:International journal of cancer 2017-01, Vol.140 (2), p.423-430
Main Authors: Polman, Nicole J., Uijterwaal, Margot H., Witte, Birgit I., Berkhof, Johannes, van Kemenade, Folkert J., Spruijt, Johan W.M., van Baal, W. Marchien, Graziosi, Peppino G.C.M., van Dijken, Dorenda K.E., Verheijen, René H.M., Helmerhorst, Theo J.M., Steenbergen, Renske D.M., Heideman, Daniëlle A.M., Ridder, Ruediger, Snijders, Peter J.F., Meijer, Chris J.L.M.
Format: Article
Language:English
Subjects:
Adult
Cancer
Cell cycle
Cellular biology
Cervical cancer
cervical cytology
Cervical Intraepithelial Neoplasia - metabolism
Cervical Intraepithelial Neoplasia - pathology
Cervical Intraepithelial Neoplasia - virology
Colposcopy - methods
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Cytodiagnosis - methods
DNA methylation
Early Detection of Cancer - methods
Female
human papillomavirus
Humans
Ki-67 Antigen - metabolism
Medical research
Middle Aged
p16/Ki‐67 dual‐stained cytology
Papillomaviridae
Papillomavirus Infections - metabolism
Papillomavirus Infections - pathology
posttreatment
Pregnancy
Prospective Studies
recurrent cervical intraepithelial neoplasia
Sensitivity and Specificity
Surveillance
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
Young Adult
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Summary:Women treated for high‐grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high‐risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki‐67 dual‐stained cytology (p16/Ki‐67) for posttreatment monitoring. Three hundred and twenty‐three women treated for high‐grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki‐67 dual‐staining was performed on residual liquid‐based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki‐67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki‐67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71–1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68–0.99). Specificity of p16/Ki‐67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19–1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12–1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki‐67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92–1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19–1.38). Thus, when considered in combination with hrHPV, p16/Ki‐67 might be an attractive approach for surveillance of women treated for high‐grade CIN. What's new? Normally the cell‐cycle regulator p16 and the proliferation marker Ki‐67 are not expressed in the same epithelial cell unless the cell is dysregulated after infection with a high‐risk human papilloma virus (hrHPV). Here the authors used p16/Ki‐67 dual‐stained cytology in combination with hrHPV testing in women treated for high‐grade intraepithelial cervical neoplasia (CIN2/3). They show that this test is as sensitive as conventional cytology/hrHPV co‐testing to detect recurrence. However, it results in lower colposcopy referrals due to higher specificity and positive predictive value, making it an interesting approach to monit
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.30449